ORAL Strategy: Tofacitinib effective in RA subset 'irrespective' of concomitant MTX
Patients with rheumatoid arthritis who achieved greater response with tofacitinib do so regardless of whether methotrexate was added to therapy or not, according to data published in Arthritis Research & Therapy.
However, among those with lower levels of response, patients who received tofacitinib monotherapy did not do as well as those on concomitant methotrexate. Overall, patients with RA demonstrated greater response with tofacitinib alongside methotrexate, compared with tofacitinib monotherapy, the researchers wrote.
“Per [American College of Rheumatology (ACR)] and EULAR guidelines, patients with RA should initiate treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate (MTX),” Tsutomu Takeuchi, MD, PhD, of Keio University, in Tokyo, Japan, and colleagues wrote. “In patients with an inadequate response to csDMARDs, it is recommended to add a biologic DMARD (bDMARD), such as a tumor necrosis factor inhibitor (TNFi), or a targeted synthetic DMARD, such as a Janus kinase (JAK) inhibitor.”
“Tofacitinib is an oral JAK inhibitor for the treatment of RA,” they added. “The phase 3b/4 ORAL Strategy study compared the efficacy and safety of tofacitinib 5 mg twice daily (BID) monotherapy, tofacitinib 5 mg BID[plus]MTX, and [adalimumab (ADA)] 40 mg every other week[plus]MTX in patients with RA and an inadequate response to MTX.”
In that study, combination therapy with tofacitinib (Xeljanz, Pfizer) and methotrexate demonstrated non-inferiority to adalimumab combination therapy based on ACR50 response rate. However, tofacitinib monotherapy failed to show non-inferiority to either combination strategy.
“The mechanism by which tofacitinib[plus]MTX provides greater efficacy than tofacitinib monotherapy is currently unknown, but is conceivably related to the effects each drug has on different mediators of inflammation,” Takeuchi and colleagues wrote.
To analyze the clinical and functional responses to tofacitinib monotherapy, tofacitinib combination therapy with methotrexate and adalimumab(Humira, AbbVie) combination therapy with methotrexate in patients with RA, Takeuchi and colleagues conducted a post-hoc analysis of data from the ORAL Strategy study. For clinical response, the researchers developed cumulative probability plots for the mean percent change from baseline in the Clinical Disease Activity Index (CDAI) at month 12. For functional response, they did the same for mean change from baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI).
The researchers included data from all 1,146 ORAL Strategy participants who received study treatment, including 384 in the tofacitinib monotherapy group, 376 who received tofacitinib alongside methotrexate and 386 treated with adalimumab plus methotrexate. In their analysis, Takeuchi and colleagues summarized median C-reactive protein (CRP) levels by time period using CDAI remission — defined as 2.8 or less — at 6 and 12 months.
According to the researchers, cumulative probability plots for mean percent change in CDAI from baseline, and mean change in HAQ-DI from baseline, were similar across all treatment strategies at 12 months in patients who demonstrated greater response. However, at lower levels of response, those who received tofacitinib monotherapy did not respond as well as those treated with either combination therapy.
Among those treated with tofacitinibplus methotrexate, patients who achieved CDAI remission at 6 and 12 months demonstrated numerically higher baseline CRP levels, and numerically larger post-baseline CRP reductions, compared with those who did not achieve CDAI remission.
“In this post hoc analysis of data from ORAL Strategy, cumulative probability plots suggest that there is a subset of patients who will achieve a deep clinical and functional response with tofacitinib treatment, irrespective of whether they receive concomitant MTX,” Takeuchi and colleagues wrote. “However, at lower levels of response, patients receiving tofacitinib monotherapy did not appear to respond as well as those receiving combination treatments. Overall, patients experienced greater response with tofacitinib[plus]MTX vs. tofacitinib monotherapy.”
“As such, tofacitinib monotherapy may be considered in patients who wish to discontinue MTX due to tolerability or toxicity issues,” they added. “However, in patients who are able to take MTX, as recommended by ACR and EULAR, tofacitinib should be added to MTX, and tapering or discontinuation of MTX should be considered only after the patient reaches their targeted disease control.”